PANCREATIC-ISLET CELLS EXPRESS A FAMILY OF INWARDLY RECTIFYING K-PROTEIN-ACTIVATED CHANNELS( CHANNEL SUBUNITS WHICH INTERACT TO FORM G)

Insulin secretion is associated with changes in pancreatic beta-cell K + permeability, A degenerate polymerase chain reaction strategy based on the conserved features of known inwardly rectifying K+ (K-IR) chann el genes was used to identify members of this family expressed in huma n pancreatic islets and insulinoma, Three related human K-IR transcrip t sequences were found: CIR (also known as cardiac KATP-1), GIRK1, and GIRK2 (KATP-2), The pancreatic islet CLR and GIRK2 full-length cDNAs were cloned, and their genes were localized to human chromosomes 11q23 -ter and 21, respectively, Northern blot analysis detected CIR mRNA at similar levels in human islets and exocrine pancreas, while the abund ance of GIRK2 mRNA in the two tissues was insufficient for detection b y this method. Using competitive reverse-transcription polymerase chai n reaction, CIR was found to be present at higher levels than GIRK2 mR NA in native purified beta-cells. Xenopus oocytes injected with M2 mus carinic receptor (M2) plus either GIRK2 or CIR cRNA expressed only ver y small carbachol-induced currents, while co-injection of CIR plus GIR K2 along with M2 resulted in expression of carbachol activated strong inwardly rectifying currents, Activators of K-ATP channels failed to e licit currents in the presence or absence of co expressed sulfonylurea receptor, These results show that two components of islet cell. K-IR channels, CIR and GIRK2, may interact to form heteromeric G-protein-ac tivated inwardly rectifying K+ channels that do not possess the typica l properties of K-ATP channels.